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Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.

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Date
2013-04
Authors
Soerensen, Mette
Dato, Serena
Tan, Qihua
Thinggaard, Mikael
Kleindorp, Rabea
Beekman, Marian
Suchiman, H Eka D
Jacobsen, Rune
McGue, Matt
Stevnsner, Tinna
Bohr, Vilhelm A
de Craen, Anton JM
Westendorp, Rudi GJ
Schreiber, Stefan
Slagboom, P Eline
Nebel, Almut
Vaupel, James W
Christensen, Kaare
Christiansen, Lene
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Abstract
In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.
Type
Journal article
Subject
Aged, 80 and over
Alleles
Apolipoproteins E
Case-Control Studies
Cholesterol Ester Transfer Proteins
Denmark
Female
Gene Frequency
Genetic Variation
Genotype
Germany
Haplotypes
Humans
Interleukin-6
Linear Models
Longevity
Longitudinal Studies
Male
Middle Aged
Netherlands
Polymorphism, Single Nucleotide
Registries
Permalink
https://hdl.handle.net/10161/14777
Published Version (Please cite this version)
10.1007/s11357-011-9373-7
Publication Info
Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea; Beekman, Marian; ... Christiansen, Lene (2013). Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. Age (Dordr), 35(2). pp. 487-500. 10.1007/s11357-011-9373-7. Retrieved from https://hdl.handle.net/10161/14777.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Vaupel

James Walton Vaupel

Research Professor in the Sanford School of Public Policy
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